Table 2.
NOTCH3 knock-in or transgenic mice.
| Mouse (Line) | Mutation (EGFr) | Transgene Expression 1 | Brain Pathology | Vascular Physiology |
|---|---|---|---|---|
| Knock-in | ||||
| Notch3R170C/R170C [78,81] | p.Arg169Cys (EGFr4) |
not applicable | N3ECD accumulation at 4 months [78]; GOM deposition at 20 months [81] | Decreased passive diameter of isolated posterior cerebral arteries at 4 months [78] |
| Human NOTCH3 cDNA driven by murine SM22a promoter | ||||
| mN3+/+; TghN3 (WT) (line 46) [82] | Wild-type | 73% | No N3ECD accumulation; no GOM deposition | ND 2 |
| mN3+/+; TghN3(R90C) (line Ma) [71,80,82] | p.Arg90Cys (EGFr 2) |
86% | N3ECD accumulation and GOM deposition at 12 months [82] | Decreased flow-induced dilatation and increased pressure-induced myogenic tone in tail caudal arteries at 10–11 months [80] |
| mN3+/+; TghN3 (C428S) (line 10) [74] | p.Cys428Ser (EGFr 10) |
150% | N3ECD accumulation and GOM deposition at 8 months [74] | ND |
| PAC 3 containing genomic locus of rat Notch3 [72,78] | ||||
| TgNotch3R169C (line 88) | p.Arg169Cys (EGFr 4) |
400% | N3ECD accumulation at 1–2 months; GOM deposition at 5 months; white matter lesion (numerous vacuoles and loss of compact myelin with disorganized fibers) at 18–20 months [72] | Reduction of resting CBF 4 in gray matter (at 11–12 months) and white matter (at 18–20 months) [72]. Impaired cerebrovascular autoregulation at 5 months and attenuated functional hyperemia at 5–6 months [72]. Decreased increment of distensibility and decreased passive diameter in isolated posterior cerebral arteries at 6 and 2 months, respectively [78] |
| TgNotch3R169C (line 92) | 200% | N3ECD accumulation and GOM deposition [25] | ND | |
| TgNotch3WT (line 129) | Wild-type | 400% | No N3ECD accumulation: no GOM deposition up to 20 months [72] | No impairment of resting CBF, cerebrovascular autoregulation, or functional hyperemia [72]. |
| BAC 5 containing genomic locus of human NOTCH3 [73,79] | ||||
| tgN3MUT (line 350) | p.Arg182Cys (EGFr 4) |
350% | N3ECD accumulation detected at 6 weeks: GOM deposition detected at 5–6 months [73]; no white matter lesion detected [73] | No functional deficit in CBF [79]. |
| tgN3MUT (line 200) | 200% | N3ECD accumulation detected at 3 months [73] | ND | |
| tgN3MUT (line 150) | 150% | N3ECD accumulation detected at 5 months [73] | ND | |
| tgN3MUT (line 100) | 100% | N3ECD accumulation detected at 12 months [73] | No functional deficit in CBF [79]. | |
| tgN3WT | Wild-type | 100% | No N3ECD accumulation; no GOM deposition up to 20 months [73] | No functional deficit in CBF [79]. |
| Human NOTCH3 cDNA, SM22-Cre mediated conditional knock-in into ROSA26 locus [75] | ||||
| NOTCH3C455R | p.Cys455Arg (EGFr 11) | ND | GOM deposition at 6 months [75] | ND |
| NOTCH3R1031C | p.Arg1031Cys (EGFr 26) |
ND | GOM deposition at 12 months [75] | ND |
1 Expression level of transgene relative to endogenous Notch3. 2 ND: not described 3 P1-derived artificial chromosome. 4 CBF: cerebral blood flow. 5 Bacterial artificial chromosome.